天津医药

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排风藤小分子化合物SCE-1对IL-6、IL-1β、TNF-α体外抑制活性研究

付雪娇,陈剑锋   

  1. 三峡大学化学与生命科学院天然产物重点实验室
  • 收稿日期:2012-08-17 修回日期:2012-10-17 出版日期:2013-02-15 发布日期:2013-02-15
  • 通讯作者: 陈剑锋

The Inhibitory Activity of a Novel Small-Molecule Inhibitor of IL-6 Signalling in vitro

FU Xue jiao,CHEN Jian feng   

  1. Hubei Key Laboratory of Natural Products Research and Development, College of Chemistry and Life Sciences, China Three Gorges University, Yichang 443002, China
  • Received:2012-08-17 Revised:2012-10-17 Published:2013-02-15 Online:2013-02-15
  • Contact: CHEN Jian feng

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摘要： 摘要 目的：探讨排风藤叔胺生物碱类小分子化合物SCE-1体外IL-6抑制活性。方法：利用细菌脂多糖（LPS）刺激经佛波酯（PMA）诱导的人单核细胞THP-1建立体外炎症模型，MTT法检测样品的细胞毒性，ELISA方法检测药物干预前后上清液中IL-6、IL-1β、TNF-α的分泌量，综合评价化合物SCE-1对炎性细胞因子和介质的抑制作用。结果：SCE-1极显著的抑制了IL-6产生，并且其抑制作用具有时间和剂量依耐性，对TNF-α也具有一定的抑制作用，对IL-1β有轻微的促进分泌作用。结论：该化合物的发现为开发高效低毒特异的小分子IL-6抑制剂提供了一个较好的先导化合物。

关键词: IL-6, 小分子抑制剂, SCE-1

Abstract:

[Abstract] Objective  To evaluate the inhibitory effects of a novel tertiary alkaloids small molecule fromSolanum cathayanum , SCE-1，on interleukin (IL-6)，IL-1β and tumor necrosis factor (TNF)-αin vitro . Methods  The inflammation modelin vitro was established by lipopolysaccharide (LPS)-stimulated phrobol 12-myristate 13-acetate (PMA)-differentiated THP-1 macrophage. The cytotoxicity of SCE-1 was determined by the mitochondrial-respiration-dependent3-(4,5-dimethylthiazol -2-yl) -2,5-diphenyltetrazolium (MTT) reduction method. The antagonism activity on proinflammatory cytokine such as IL-6, IL-1β and TNF-α in cell culture medium were determined by enzyme-linked immunosorbent assay (ELISA) method. The inhibitory effect on proinflammatory cytokine of compounds SCE-1 was evaluated. Results  Compared with the control group，(1) the SCE-1(12.5~800 mg/L) showed a significant inhibitory effect in dose- and time-dependent manner on the production of IL-6 (P < 0.01) with an IC50 of 11.82 mg/L; (2) the SCE-1 (200~800 mg/L) decreased the production of TNF-α (P < 0.05 or P < 0.01), and the inhibition rate was 53.13% at a concentration of 800 mg/L and for 2-h treatment; (3) the SCE-1 (400~800 mg/L) significantly increased the production of IL-1β (P < 0.01). Conclusion  The discovery of this com pound provided a potential lead compound for the development of small molecule IL-6 inhibitor with high efficiency and low toxicity.

Key words: IL-6, small antagonists, SCE-1